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Cited by 4Liver physiology and pathologyTissue Engineering and Regenerative MedicineOrgan Transplantation Techniques and Outcomes

Second harmonic generation microscopy reveals the spatial orientation of glutamine-potentiated liver regeneration after hepatectomy

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Yen, Chih-Chieh, Yen, Chia-Sheng, Tsai, Hung-Wen, Yeh, Matthew M., Hong, Tse-Ming, Wang, Wen-Lung, Liu, I-Ting, Shan, Yan-Shen +1 more·2025·Hepatology Communications
DOI 10.1097/hc9.0000000000000640PMC PMC11888978
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Abstract

Background: Glutamine (Gln) is a critical amino acid for energy expenditure. It participates in extracellular matrix (ECM) formation and circulates in the hepatic parenchyma in a spatial-oriented manner. Posthepatectomy liver mass recovery poses a regenerative challenge. However, little is known about the role of Gln in liver regeneration, notably the spatial orientation in the remodeling process. This study aimed to elucidate Gln-potentiated liver regeneration and ECM remodeling after mass loss. Methods: We studied the regenerative process in hepatectomized mice supplemented with Gln. Second harmonic generation/two-photon excitation fluorescence microscopy, an artificial intelligence–assisted structure-based imaging, was used to demonstrate the spatial-oriented process in a hepatic acinus. Results: Gln promotes liver mass regrowth through the cell cycle, Gln metabolism, and adipogenesis pathways after hepatectomy. Ornithine transaminase, one of the upregulated enzymes, showed temporal, spatial, and functional correspondence with the regeneration process. Second harmonic generation/two-photon excitation fluorescence microscopy highlighted transient hepatic steatosis and ECM collagen synthesis, predominantly in the portal tract instead of the central vein area. Structural remodeling was also observed in the portal tract area. Conclusions: Gln promotes liver regeneration through cellular proliferation and metabolic reprogramming after hepatectomy. Using structure-based imaging, we found that Gln potentiated hepatic steatosis and ECM collagen deposition predominantly in the portal tract area. These results highlighted the spatial orientation and mechanistic implications of Gln in liver regeneration.

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  • Hepatic steatosis is more pronounced in glutamine-supplemented animals, indicating a regenerative adaptation response.

    “Hepatic steatosis was also more pronounced in these animals, indicating a regenerative adaptation response[68].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [68]

  • Collagen deposition within the extracellular matrix significantly increases in glutamine-supplemented mice, particularly in the portal tract region.

    “Additionally, collagen deposition within the ECM significantly increased in glutamine-supplemented mice, particularly in the portal tract region.”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [68]

  • In C57BL/6 mice undergoing 70% hepatectomy, 0.6% glutamine-enriched water before and after surgery accelerates liver mass recovery, particularly between 2 and 4 days after intervention.

    “In studies using C57 Black 6 (C57BL/6) mice undergoing 70% hepatectomy, animals that received 0.6% Gln-enriched water before and after surgery exhibited accelerated liver mass recovery, particularly between 2 and 4 days after intervention.”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [68]

  • OAT activation links glutamine metabolism to ammonia detoxification and extracellular matrix remodeling.

    “Further analysis revealed that OAT activation linked glutamine metabolism to ammonia detoxification and ECM remodeling[68].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [68]

  • Liver regeneration following partial hepatectomy is a complex and highly coordinated process involving hepatocyte proliferation, extracellular matrix reorganization, and metabolic remodeling.

    “LR following PH is a complex and highly coordinated process involving hepatocyte proliferation, ECM reorganization, and metabolic remodeling[68].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [68]

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Cited by

Sorted by citations

Authors
Yen, C.-C., Yen, C.-S., Tsai, H.-W., Yeh, M. M., Hong, T.-M., Wang, W.-L., Liu, I.-T., Shan, Y.-S., & Yen, C.-J.
Affiliations
  • Kaohsiung Veterans General Hospital (TW)
  • National Cheng Kung University Hospital (TW)
  • University of Washington (US)
  • National Cheng Kung University (TW)
Corresponding author
  • Yen, Chih-Chieh
  • Yen, Chia-Sheng
  • Yen, Chia-Jui
ORCID
Venue
Hepatology Communications
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2025-03
Volume
9
Issue
3
ISSN
2471-254X (ISSN-L)
DOI
10.1097/hc9.0000000000000640
PMC
PMC11888978
OpenAlex
W4408182439
Cited by
4
References
2
Citations by year
2026: 3 · 2025: 1
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
glutamine, liver regeneration, hepatectomy, extracellular matrix remodeling, collagen deposition, hepatic steatosis, ornithine aminotransferase, hepatic acinus, portal tract, adipogenesis, metabolic reprogramming, cell cycle
MeSH terms
Second Harmonic Generation Microscopy, Animals, Extracellular Matrix, Glutamine, Hepatectomy, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Multiphoton, Cell Proliferation, Mice

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